CD36-Mediated Lipid Metabolic Reprogramming in Hepatocellular Carcinoma: Crosstalk With Immunity, Ferroptosis, and Therapeutic Resistance.
- 1Department of General Surgery, Yangzhou University, Yangzhou, CHN.
- 2Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, CHN.
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death and is associated with metabolic dysfunction and chronic liver disease. Lipid metabolic reprogramming is a key hallmark of HCC, and CD36, a fatty acid translocase and scavenger receptor, has emerged as a central regulator of this process. This review investigated the multifaceted roles of CD36 in HCC pathogenesis. CD36 facilitates long-chain fatty acid uptake and affects oncogenic signaling and the tumor immune microenvironment. CD36-mediated lipid accumulation promotes cytotoxic T-cell function and macrophage M2 polarization and drives immune evasion. Likewise, CD36 modulates ferroptosis sensitivity by influencing polyunsaturated fatty acid-induced lipid peroxidation and redox balance. Through metabolic plasticity and oxidative stress adaptation, CD36 also contributes to resistance to chemotherapy, targeted therapies, and immunotherapy. In conclusion, CD36 serves as a critical multifunctional regulator linking lipid metabolism, ferroptosis, immunomodulation, and therapy resistance in HCC, positioning it as a promising therapeutic target for improving clinical outcomes. However, clinical translation remains challenging due to the broad tissue expression of CD36 and the lack of large-scale clinical validation. Hence, future research should focus on clinical validation of CD36, mechanistic elucidation, selective inhibitor development, combination therapy evaluation, and multi-omics-guided personalized HCC treatment.
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BibTeX
@article{bijaraniya2026cd36mediated,
title = {{CD36-Mediated Lipid Metabolic Reprogramming in Hepatocellular Carcinoma: Crosstalk With Immunity, Ferroptosis, and Therapeutic Resistance.}},
author = {Ankit Kumar Bijaraniya and Tao Lide},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116886},
url = {https://europepmc.org/article/MED/42928736},
note = {CC BY},
}
RIS
TY - JOUR
TI - CD36-Mediated Lipid Metabolic Reprogramming in Hepatocellular Carcinoma: Crosstalk With Immunity, Ferroptosis, and Therapeutic Resistance.
AU - Ankit Kumar Bijaraniya
AU - Tao Lide
PY - 2026
DA - 2026/09/25
JO - Cureus
DO - 10.7759/cureus.116886
UR - https://europepmc.org/article/MED/42928736
AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer death and is associated with metabolic dysfunction and chronic liver disease. Lipid metabolic reprogramming is a key hallmark of HCC, and CD36, a fatty acid translocase and scavenger receptor, has emerged as a central regulator of this process. This review investigated the multifaceted roles of CD36 in HCC pathogenesis. CD36 facilitates long-chain fatty acid uptake and affects oncogenic signaling and the tumor immune microenvironment. CD36-mediated lipid accumulation promotes cytotoxic T-cell function and macrophage M2 polarization and drives immune evasion. Likewise, CD36 modulates ferroptosis sensitivity by influencing polyunsaturated fatty acid-induced lipid peroxidation and redox balance. Through metabolic plasticity and oxidative stress adaptation, CD36 also contributes to resistance to chemotherapy, targeted therapies, and immunotherapy. In conclusion, CD36 serves as a critical multifunctional regulator linking lipid metabolism, ferroptosis, immunomodulation, and therapy resistance in HCC, positioning it as a promising therapeutic target for improving clinical outcomes. However, clinical translation remains challenging due to the broad tissue expression of CD36 and the lack of large-scale clinical validation. Hence, future research should focus on clinical validation of CD36, mechanistic elucidation, selective inhibitor development, combination therapy evaluation, and multi-omics-guided personalized HCC treatment.
SN - 2168-8184
ER -